Compound 3l

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

N-bromosuccinimide (NBS, 2.56 g, 14.4 mmol) was added to a solution of dithiane 8 ((a) Paulsen, H.; Schüller, M.; Heitmann, A.; Nashed, M. A.; Redlich, H. Liebigs Ann. Chem., 1986, 675, (1986); (b) Krohn, K.; Börner, G. J. Org. Chem., 59, 6063, (1994)) (607 mg, 1.44 mmol) and NaHCO₃ (605 mg, 7.20 mmol) in MeCN (5.4 mL) and H₂O (1.8 mL) at 0 °C. The reaction mixture was stirred for 20 min at room temperature, and then saturated aqueous NaHCO₃ (10 mL) and saturated aqueous Na₂S₂O₃ (20 mL) were successively added at 0 °C. The resultant mixture was extracted with CHCl₃ (20 mL x3). The combined organic layers were washed with saturated aqueous Na₂CO₃ (30 mL x3) and brine (30 mL), dried over Na₂SO₄, filtered and concentrated to afford the crude aldehyde S14 (525 mg), which was used in the next reaction without further purification. NaClO₂ (650 mg, 7.19 mmol) was added to a solution of the above crude aldehyde S14 (525 mg) and NaH₂PO₄·2H₂O (2.25 g, 14.4 mmol) in 2-methyl-2-butene (5.0 mL), t-BuOH (4.8 mL) and H₂O (2.4 mL) at room temperature. The reaction mixture was stirred for 20 h at room temperature, and then brine (20 mL) was added. The resultant mixture was extracted with CHCl₃ (20 mL x3). The combined organic layers were dried over Na₂SO₄, filtered and concentrated. The residue was purified by flash column chromatography on silica gel (15 g, hexane/EtOAc 3/1 to 0/1) to afford carboxylic acid 3l (473 mg, 1.37 mmol) in 95% yield over 2 steps: colorless solid; mp 57-58 °C; [α]_D²⁴ = +4.99 (c 1.00, CHCl₃); IR (film) 3460, 3174, 2988, 2938, 1734, 1383, 1373, 1215, 1156, 1068 cm^-1; ¹H NMR (400 MHz, CDCl₃) δ 1.34 (3H, s, CH₃ of acetonide), 1.39 (3H, s, CH₃ of acetonide), 1.40 (3H, s, CH₃ of acetonide), 1.42 (3H, s, CH₃ of acetonide), 1.44 (3H, s, CH₃ of acetonide), 1.50 (3H, s, CH₃ of acetonide), 3.98 (1H, m, H6_A), 4.03 (1H, m, H4), 4.08-4.17 (2H, m, H5, 6_B), 4.24 (1H, dd, J = 6.3, 3.6 Hz, H3), 4.51 (1H, dd, J = 6.3, 3.6 Hz, H2), 4.71 (1H, d, J = 6.3 Hz, H1), 8.10 (1H, br s, CO₂H); ¹³C NMR (100 MHz, CDCl₃) δ 25.2, 25.8, 26.3, 26.8, 27.1, 27.4, 67.3, 74.8, 76.7, 78.0, 79.0, 79.9, 109.9, 110.4, 112.2, 175.3; HRMS (ESI) calcd for C₁₆H₂₆O₈Na [M+Na]⁺ 369.1520, found 369.1509.